Recent trends in mass spectrometer design have included the development of “brighter” ion sources capable of generating and delivering large numbers of ions to downstream components of the mass spectrometer for mass analysis. Improvements in ion sources have included high-throughput ion transfer tubes, which possess higher gas conductances relative to prior designs while maintaining adequate heat transfer for evaporation of residual solvent, and radio-frequency (RF) optics located within the source regions, such as ion funnels or S-lenses, which enable effective focusing of ions to an axial centerline. While these and other improvements have produced significant benefits in terms of increased instrument sensitivity (e.g., the ability to detect and measure ever smaller quantities of analytes), the use of brighter ion beams has the disadvantage of causing fouling of mass spectrometer components more quickly relative to predecessor designs. As the surfaces of these components become contaminated, charging and other operational problems arise, eventually requiring the instrument to be cleaned to restore its performance. The need to frequently clean the components of a mass spectrometer increases instrument downtime and is thus disfavored, particularly since the cleaning procedure typically requires that the vacuum chambers be vented to atmosphere, in turn necessitating a lengthy pump-down period before the instrument may again be used for sample analysis.
In order to alleviate the contamination problem associated with brighter ion sources, and to decrease the frequency at which cleaning must be performed, some instruments (e.g., the Q Exactive Plus mass spectrometer available from Thermo Fisher Scientific) have incorporated ion filtering strategies in which unwanted ions are rejected early in the ion pathway. Referring initially to FIG. 1, which symbolically depicts components in the source region of a mass spectrometer, a heated capillary (alternatively referred to as an ion transfer tube) 110 extends between an atmospheric pressure region and a first vacuum region 120 operated at reduced pressure. A not-depicted electrospray ionization (ESI) or atmospheric-pressure chemical ionization (APCI) source located in the atmospheric-pressure region may be employed to generate ions from a sample (e.g., the eluate of a liquid chromatograph). A portion of the ions thus formed enter the front end of the ion transfer tube and are conveyed through the tube by gas dynamic (and/or electrostatic) forces. Ion transfer tube 110 may be heated so as to evaporate residual liquid solvent. Ions, together with background gas, leave the ion transfer tube through the back end thereof as a free jet that expands into first vacuum region 120. An ion funnel 130 may be employed to focus the ions to an axial flow centerline while permitting the removal of gas through a vacuum pump port. As is known in the art, ion funnel 130 consists of a stacked ring ion guide having apertures of progressively smaller dimension in the direction of ion flow, with RF voltages applied in alternating phases to successive ring electrodes to generate an RF field that urges ions toward the axial centerline. Alternative structures, such as an S-lens (a stacked ring ion guide having longitudinal spacing between ring electrodes increasing in the flow direction) may be used in place of the ion funnel.
The vacuum pressures in the first and second vacuum regions 120 and 140 may be established and controlled via the use of a set of vacuum pumps (typically including a combination of mechanical pumps and/or turbomolecular pumps) that communicates with the vacuum regions via respective ports.
Downstream of ion funnel 130 (or other optic) is a lens 150 that divides first vacuum region 120 from second vacuum region 140. Lens 150 has a conductance-limited aperture that permits the second vacuum region to be maintained at a lower pressure than the first vacuum region. Located inside second vacuum region 140 is a short (relative to conventional quadrupole mass filters used as mass analyzers) RF/DC ion guide 160, alternately referred to herein as a pre-filter or source filter. In this particular configuration, source filter 160 is comprised of four elongated rod electrodes. Following this source filter is another lens 170 having a conductance-limited aperture. The second lens of the mass spectrometer source region can be followed by many possible mass spectrometer configurations, comprising ion guides, mass analyzers, collision cells, lenses, etc.
To enable filtering of ions based on their mass-to-charge ratio (m/z), a voltage source (not depicted) is configured to apply oscillatory (i.e., radio-frequency (RF)) and resolving DC voltages to the rod electrodes. In this implementation, an RF voltage with a low amplitude (to avoid breakdown and consequent arcing in the relatively high-pressure vacuum regions) and a high frequency (to facilitate ion focusing) is applied to the electrodes of source filter 160. Ion trajectories are often described as stable or instable based upon their location on the Mathieu stability diagram. Based upon the electric fields applied to source filter 160 (i.e., low RF amplitude and high frequencies), the ions will tend to reside at very low q-values on the Mathieu stability diagram while they are in the source filter region. As such, source filter 160 will be practically limited to acting as a low-pass ion filter.
The environmental conditions in the source region of the mass spectrometer deviate substantially from what is typically found in a vacuum chamber containing a conventional quadrupole mass filter mass analyzer. In the embodiment depicted in FIG. 1 and described above, both the vacuum pressure in the source region and the physical space available constrain the performance of source filter 160. Depending upon the vacuum pumps on the system, the size of the gas conductance limits (e.g., the apertures size of lenses 150 and 170), and the gas flow rate through the heated capillary, the pressure in second vacuum region 140 can vary from a few mTorr to greater than 100 mTorr. Also, the need to limit the instrument footprint, in conjunction with the differential pumping requirements in the source region, work together to constrain the length of the RF/DC ion guide in second vacuum region 140 (typically to less than 30 mm).
High-quality quadrupole mass filters may be constructed from four elongated rod electrodes having truncated hyperbolic surfaces facing the ion flow centerline. This geometry minimizes departures from an ideal purely quadrupolar field that adversely impact device performance. As a lower cost alternative, four round rod electrodes (cylindrical electrodes having circular cross-sections) are often substituted for the hyperbolic rods. The arrangement of cylindrical rod electrodes to form a quadrupole mass filter is depicted in perspective view in FIG. 2. The rod electrodes extend parallel to an axial centerline 210 between an inlet end 220 that accepts ions to be filtered and an outlet end 230 from which the selectively transmitted ions exit the mass filter. FIG. 3, which shows a cross-sectional view of the quadrupole mass filter taken through a lateral plane (labeled as A-A in FIG. 2) directed transverse (i.e., perpendicular) to axial centerline 210, shows that each rod electrode (labeled 310a-d) is positioned at a distance r0 from the axial centerline (this distance r0 being referred to as the inscribed radius), and that the rods are arranged in two pairs, with each pair being aligned to and opposed across the centerline such that the centers of the rod cross-sections define the vertices of a square. The rods may be of equal cross-sectional radii r. Though these simpler, non-ideal rod geometries are easier to construct, they can introduce higher order multipole fields (e.g., A6 and A10 field components) that may hamper filter performance. A number of references in the mass spectrometry literature have sought to identify an optimal value of the ratio (r/r0) between the radius of the rods and the radius of the inscribed circle defined by the inner surfaces of the rods that minimizes the magnitude and overall effect of these higher order multipole potentials. Depending upon how this “optimal” ratio is determined, the value tends to fall between 1.14 and 1.16, and virtually all of the commercially available round-rod quadrupole mass filters have geometries that fall within this range.
The performance of the source filter in the source region is closely tied to the pressures in those vacuum chambers. By adjusting the throughput of the vacuum pumps, it is possible to vary the pressures in these vacuum regions. Measurements of the transmission profile of an exemplary ion (formed from the Ultramark® 1022 reference compound) using a source filter with an r/r0 ratio of 1.148 revealed that as the pressure in the source region increases, the boundary between instable and stable ion trajectories (i.e., the slope between 0 and 100% transmission efficiency) distorts and becomes shallower. At higher pressure, the ions will undergo increased collisional damping such that it becomes harder to remove unwanted ions from of the ion beam within the short duration of the source filter. A perfect ion filter will transmit 100% of the desired ions while rejecting 100% of the unwanted species. A broad transitional region indicates that it will be difficult to find such a discrete boundary at which we reject all the unwanted ions while retaining all the desired species. In this way, source filter performance is directly related to the slope of this transitional region. As the slope of this transitional region increases, so does the performance of the source filter. In this context, the pronounced negative relationship between source pressure and source filter performance for the standard r/r0 ratio is concerning.